LP-168 (Rocbrutinib), a Novel Covalent and Non-Covalent Next-Generation Inhibitor of Bruton's Tyrosine Kinase. Phase 1 trial results.

[Jm954]

Rocbrutinib is a new drug offering hope to patients with what are known as gatekeeper mutations that confer resistance to Pirtobrutinib. This BTKi is unique in being both a covalent and non covalent inhibitor of BTK.

Patients with gatekeeper mutations have poor outcomes and short survival and demonstrate an increasing unmet need in the field of CLL.

Second-site T474 gatekeeper mutations have been commonly observed in patients resistant to non covalent BTKi such as pirtobrutinib. LP-168 (rocbrutinib) is a selective next generation inhibitor of BTK that targets wild type (WT) BTK irreversibly, C481 mutant BTK (C481S, C481F and C481R) reversibly, and other non-C481 mutations such as gatekeeper mutation T474I irreversibly,

Overall, the trial has enrolled 50 DLT-evaluable pts. CLL pts make up 47 of them and now have efficacy data. The estimated 18-month progression free survival (PFS) rate of CLL pts is 68.5% (95% CI 44.1 - 83.9%). For 22 CLL pts with starting doses ≥ 200mg, the ORR is 77.3% (17/22) with median follow-up of 13.95 months (range 2.5-23.3). There was no new safety signals to report.

More details here: ashpublications.org/blood/a...

and here: vjhemonc.com/video/oamsrn0p...

Jackie

[ABP45UK]

Thank you for posting Jackie and, as always, keeping us all well informed.

[mrsjsmith]

Thank you Jackie,

Gatekeeper mutations, another phrase that’s new to me.

Assume Rocbrutinib isn’t approved by Nice yet ?

Colette

[Justasheet1]

Jackie,

You can add a link to your post for ClL Society. Dr. Koffman highlights it on his website.

Jeff

[Jm954 Administrator in reply to Justasheet1]

I didn’t know about the CLL Society information.

[Justasheet1]

cllsociety.org/2024/06/safe...

[Jm954 Administrator in reply to Justasheet1]

thank you!

[Shepherd777]

Great to know they are making progress for treating those with resistance mutations.

[Skyshark]

If the PFS holds up it might have a median of 28 months.

The next question to answer is, does it have a longer overall median (28+16.9) if pirtobrutinib isn't used?

[Bluesinthenight]

Interesting agent and early phase I results for the subgroup of relapsed/resistant GM CLL patients, with median follow-up of about 14 months for the entire group enrolled. Encouraging that further development is planned and underway. Looking forward to seeing the results with longer follow-up. Thank you for posting!

[LeoPa]

Could this be even more beneficial for treatment naive patients? Less side effects, attack the enemy on two fronts at the same time.

[Jm954 Administrator in reply to LeoPa]

It would have a long way to go before it would be considered for treatment naive patients as it's still in phase 1 or the safety phase of clinical trials. It looks promising though